Thermostable particle-based compositions and manufacturing process

Abstract

Compositions and methods of using the same wherein the compositions include particles comprising one or more materials soluble in a solvent that is suitable for spray drying and one or more antigenic and/or non-antigenic payloads entrapped within the particles, wherein the composition is stable at room temperature for at least six months.

What is claimed is: 
     
         1 . A method for manufacturing particle-based compositions comprising the steps of:
 i) reducing a lyophilized antigenic and/or a non-antigenic payload to an average size of about 10 nanometers to about 1500 nanometers in the presence of a first solvent to form a payload suspension;   ii) mixing the payload suspension with a solution to form a mixture, wherein the solution comprises a material soluble in a second solvent, wherein the second solvent comprises a solvent suitable for spray drying; and   iii) spray drying the mixture to form the particle-based composition.   
     
     
         2 . The method of  claim 1 , wherein the reducing step comprises milling or grinding the lyophilized antigenic or the non-antigenic payload. 
     
     
         3 . The method of  claim 2 , wherein the reducing step comprises milling, and the milling comprises wet milling. 
     
     
         4 . The method of  claim 1 , wherein the first solvent and the second solvent comprise one or more of an alcohol, a halogenated hydrocarbon, an aliphatic hydrocarbon, an aromatic hydrocarbon, a ketone, an ester, an ether, a nitrile, an amide, and acid, and a base. 
     
     
         5 . The method of  claim 4 , wherein the first solvent and the second solvent comprise one or more of ethanol, chloroform, acetone, dichloromethane, acetonitrile, ethyl acetate, isopropanol, acetic acid, benzene, 2-butanone, n-butanol, butyl acetate, carbon tetrachloride, cyclohexane, 1,2-dichloroethane, diethyl ether, di-isopropyl ether, dimethylformamide, dimethyl sulfoxide, dioxane, heptane, hexane, isooctane, methanol, methyl ethyl ketone, methyl-t-butyl ether, pentane, n-propanol, tetrahydrofuran, toluene, trichloroethylene, water, and xylene. 
     
     
         6 . The method of  claim 4 , wherein the first solvent and the second solvent comprise one or more of ethanol, chloroform, acetone, dichloromethane, acetonitrile, ethyl acetate, and isopropanol. 
     
     
         7 . The method of  claim 1 , wherein a concentration of the antigen or the non-antigenic payload in the milled suspension is about 0.1 mg/mL to about 500 mg/mL. 
     
     
         8 . The method of  claim 1 , wherein a concentration of the material in the mixture is about 0.1 mg/mL to about 500 mg/mL. 
     
     
         9 . The method of  claim 1 , wherein the antigenic payload comprises a protein, a peptide, a nucleic acid, or a small molecule; and/or
 the non-antigenic payload comprises one or more of an adjuvant, a protein, peptide, nucleic acid, small molecule, pharmaceutical drug, bacteria, virus, and whole cell lysate.   
     
     
         10 . The method of  claim 9 , wherein the antigenic payload comprises one or more of influenza virus hemagglutinin (HA), influenza virus nucleoprotein (NP), influenza virus neuraminidase (NA), influenza matrix proteins (M), RSV pre- or post-fusion F protein, RSV G protein, or SARS-COV-2 spike protein(S), SARS-COV-2 nucleocapsid (N), SARS-COV-2 membrane protein (M), SARS-COV-2 envelope (E) protein,  Yersinia pestis  fusion protein F1-V, and  Bacillus anthracis  protective antigen (PA). 
     
     
         11 . The method of  claim 9 , wherein the non-antigenic payload comprises the adjuvant, wherein the adjuvant is entrapped within the particles, wherein the adjuvant comprises at least one of a CpG oligodeoxynucleotide (CpG ODN), a Toll-like receptor (TLR) agonist, a nucleotide oligomerization domain (NOD)-like receptor (NLR) agonist, a RIG-like receptor (RLR), a liposome, an aluminum salt, a mineral salt, an oil emulsion, a polymer, a polysaccharide, a saponin, cyclic dinucleotides, and a Stimulator of Interferon Genes (STING) activating adjuvant. 
     
     
         12 . The method of  claim 1 , wherein the material comprises polymers or homopolymers comprising one or more of polyanhydrides, poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), poly(glycerol sebacate) (PGS), PEG-PCL, polyhydroxyalkanoates (PHA), polyethylene (PE), poly(methyl methacrylate) (PMMA), polytetrafluoroethylene (PTFE), silicone, polyurethane, Poly(N-isopropylacrylamide) (PNIPAAm), poly(acrylic acid) (PAA), collagen, chitosan, alginate, hyaluronic acid, chondroitin sulfate, and gelatin. 
     
     
         13 . The method of  claim 12 , wherein the material comprises homopolymers or copolymers comprising an average molecular weight of about 5,000 g/mol to about 30,000 g/mol. 
     
     
         14 . The method of  claim 1 , wherein the material comprises:
 i) a CPTEG:CPH copolymer;   ii) a CPTEG:SA copolymer;   iii) a CPH:SA copolymer;   iv) a CPTEG homopolymer;   v) a CPH homopolymer;   vi) a SA homopolymer;   vii) a PLGA copolymer;   viii) a PLA homopolymer;   ix) a PGA homopolymer, or   x) a polymer other than a polyanhydride that is soluble in a solvent suitable for spray drying.   
     
     
         15 . A composition manufactured according to the method of  claim 1 . 
     
     
         16 . A composition comprising:
 particles comprising one or more materials soluble in a solvent suitable for spray drying; and   one or more antigenic and/or non-antigenic payloads entrapped within the particles; wherein the one or more antigenic and/or the non-antigenic payloads have an average size of about 10 nm to about 1500 nm;   wherein the particles have an average particle size of about 0.15 μm to about 10 μm.   
     
     
         17 . The composition of claim  17 , wherein the one or more materials comprise one or more of a biodegradable material, a nonbiodegradable material, a chemically degradable material, a stimuli-responsive material, a water-soluble material, and a swellable material. 
     
     
         18 . The composition of  claim 17 , wherein the material comprises one or more of polyanhydrides, poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), poly(glycerol sebacate) (PGS), PEG-PCL, polyhydroxyalkanoates (PHA), polyethylene (PE), poly(methyl methacrylate) (PMMA), polytetrafluoroethylene (PTFE), silicone, polyurethane, Poly(N-isopropylacrylamide) (PNIPAAm), poly(acrylic acid) (PAA), collagen, chitosan, alginate, hyaluronic acid, chondroitin sulfate, and gelatin. 
     
     
         19 . The composition of  claim 16 , wherein the material comprises homopolymers or copolymers comprising an average molecular weight of about 5,000 g/mol to about 30,000 g/mol. 
     
     
         20 . The composition of  claim 16 , wherein the solvent suitable for spray drying comprises one or more of chloroform, dichloromethane, ethanol, acetone, acetonitrile, ethyl acetate, isopropanol, acetic acid, acetonitrile, benzene, 2-butanone, n-butanol, butyl acetate, carbon tetrachloride, cyclohexane, 1,2-dichloroethane, diethyl ether, di-isopropyl ether, dimethylformamide, dimethyl sulfoxide, dioxane, heptane, hexane, isooctane, methanol, methyl ethyl ketone, methyl-t-butyl ether, pentane, n-propanol, tetrahydrofuran, toluene, trichloroethylene, water, and xylene. 
     
     
         21 . The composition of  claim 20 , wherein the solvent suitable for spray drying comprises one or more of chloroform, dichloromethane, ethanol, acetone, acetonitrile, ethyl acetate, and isopropanol. 
     
     
         22 . The composition of  claim 16 , wherein the antigenic payload comprises a eukaryotic, a prokaryotic, or viral antigen. 
     
     
         23 . The composition of  claim 22 , wherein the antigenic payload comprises one or more of influenza virus hemagglutinin (HA), influenza virus nucleoprotein (NP), influenza virus neuraminidase (NA), influenza matrix proteins (M), RSV pre- or post-fusion F protein, RSV G protein, or SARS-COV-2 spike protein(S), SARS-COV-2 nucleocapsid (N), SARS-COV-2 membrane protein (M), SARS-COV-2 envelope (E) protein,  Yersinia pestis  fusion protein F1-V, and  Bacillus anthracis  protective antigen (PA). 
     
     
         24 . The composition of  claim 17 , wherein the non-antigenic payload comprises the adjuvant, wherein the adjuvant is entrapped within the particles, wherein the adjuvant is a CpG oligodeoxynucleotide (CpG ODN), a Toll-like receptor (TLR) agonist, a nucleotide oligomerization domain (NOD)-like receptor (NLR) agonist, a RIG-like receptor (RLR), a liposome, an aluminum salt, a mineral salt, an oil emulsion, a polymer, a polysaccharide, a saponin, a cyclic dinucleotide, or a Stimulator of Interferon Genes (STING) activating adjuvant. 
     
     
         25 . The composition of  claim 18 , wherein the material comprises polyanhydrides, and the particles are stable at room temperature for at least 6 months, wherein the polyanhydrides are selected from the group consisting of:
 i) a CPTEG:CPH copolymer;   ii) a CPTEG:SA copolymer;   iii) a CPH:SA copolymer;   iv) a CPTEG homopolymer;   v) a CPH homopolymer; and   vi) a SA homopolymer.